Interleukin-1 receptor signaling rather than that of tumor necrosis factoris critical in protecting the host from the severe consequences of a polymicrobe anaerobic infection

Infection of the dental pulp leads to an osteolytic lesion that results fro m a polymicrobial infection consisting largely of pathogenic anaerobes. Inf ection causes significant morbidity and mortality mediated by bacterial fac tors and in some cases by the up-regulation of inflammatory cytokines. The inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) , in particular, play a complex and central role in the responses to microb ial pathogens. However, relatively little is known about the significance o f these cytokines in protecting the host from focal polymicrobial anaerobic infections. To establish the relative importance of IL-1 and TNF in mediat ing the response to a mixed anaerobic infection, we inoculated the dental p ulp of mice with six anaerobic pathogens containing functional deletions of receptors to IL-1 (IL-1R1(-/-)), TNF (TNFRp55(-/-)-p75(-/-)), or both (TNF Rp55(-/-)-IL-1RI(-/-)), The results indicate that IL-1 receptor signaling a nd TNF receptor signaling both play similarly important roles in protecting the host from local tissue damage. However, IL-1 receptor signaling is con siderably more important than TNF receptor signaling in preventing the spre ad of infection into surrounding fascial planes, since IL-1R1(-/-) but not TNFRp55(-/-)-p75(-/-) mice exhibited significantly higher morbidity and mor tality. Moreover, all of the fatal infections occurred in male mice, sugges ting the importance of gender differences in limiting the impact of these i nfections.